Cancer is caused by rapidly dividing cells. It is a major cause of morbidity and mortality. Cancer arises from a tissue/organ. In spite of the fact that it arises from a single tissue/organ, the cells are not identical (homologous). Cancer is being treated by surgical removal, radiotherapy and/or chemotherapy. The passive immunotherapy in form of antibodies is also found to be useful. Presence of heterogeneous cells in a cancer arising from a single tissue/organ is known to be responsible to poor response to cancer therapies other than surgical therapy. These are more important for treating the cancers using immunotherapy.
Active immunotherapy is being tried in form of vaccine for management of cancer. Active immunotherapy requires use of antigen specific to cancer being treated. Some of the Cancer specific antigens include matrix metalloproteinase inhibitors, epidermal growth factor, gastrin, whole cancer cells, Heat Shock Proteins etc.
Several methods have been proposed for producing immunogenic cancer vaccine using whole cells. The immune response generated by cancer vaccine often causes autoimmunity or toxicity (Blood-2011-01-325-266).
Thus there is a need to have cancer antigen which induces immune response against cancer antigens but not against normal cells (Autoimmunity).
Cancer cells when used as an antigen either lack immunogenicity or generate poor immune response. It is known that anthracyclin and Oxliplatin improves immunogenicity of cancer cells as reported by Laurence Zitvogel et al in Clin Cancer Res, 2010, 16(12):3100-4. “In response to some chemotherapeutic agents (such as anthracyclines and oxaliplatin) and ionizing irradiation, tumor cells undergo immunogenic apoptosis, meaning that they trigger a protective immune response when they are injected subcutaneously in the absence of any adjuvant into immunocompetent mice (J Exp Med 2005; 202: 1691-701; Nat Med 2007; 13: 54-61; Immunol Rev 2007; 220: 22-34; Nat Med 2007; 13: 1050-9; Nat Med 2009; 15:1170-8; Cell Mol Immunol 2009; 6: 469-75; Cancer Immunol Immunother 2010; 59: 769-77.) In contrast, cells succumbing in response to other anticancer drugs (such as alkylating agents and cisplatin) fail to trigger such an immune reaction (J Exp Med 2005; 202: 1691-701.).”
The challenge is to generate the immune response specific against cancer cells without being reactive to normal cells and cancer cells of different tissue/organ of origin.
Thus there is an unmet need to provide a cancer vaccine having immunogenicity to the heterogeneous population of cells originating from same tissue/organ with no reactivity to the normal cells.